Abstract and Introduction

Abstract

Background: Approaches to controlling emerging antibiotic resistance in health care settings have evolved over time. When resistance to broad-spectrum antimicrobials mediated by extended-spectrum β-lactamases (ESBLs) arose in the 1980s, targeted interventions to slow spread were not widely promoted. However, when Enterobacteriaceae with carbapenemases that confer resistance to carbapenem antibiotics emerged, directed control efforts were recommended. These distinct approaches could have resulted in differences in spread of these two pathogens. CDC evaluated these possible changes along with initial findings of an enhanced antibiotic resistance detection and control strategy that builds on interventions developed to control carbapenem resistance.

Methods: Infection data from the National Healthcare Safety Network from 2006–2015 were analyzed to calculate changes in the annual proportion of selected pathogens that were nonsusceptible to extended-spectrum cephalosporins (ESBL phenotype) or resistant to carbapenems (carbapenem-resistant Enterobacteriaceae [CRE]). Testing results for CRE and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are also reported.

Results: The percentage of ESBL phenotype Enterobacteriaceae decreased by 2% per year (risk ratio [RR] = 0.98, p<0.001); by comparison, the CRE percentage decreased by 15% per year (RR = 0.85, p<0.01). From January to September 2017, carbapenemase testing was performed for 4,442 CRE and 1,334 CRPA isolates; 32% and 1.9%, respectively, were carbapenemase producers. In response, 1,489 screening tests were performed to identify asymptomatic carriers; 171 (11%) were positive.

Conclusions: The proportion of Enterobacteriaceae infections that were CRE remained lower and decreased more over time than the proportion that were ESBL phenotype. This difference might be explained by the more directed control efforts implemented to slow transmission of CRE than those applied for ESBL-producing strains. Increased detection and aggressive early response to emerging antibiotic resistance threats have the potential to slow further spread.

Introduction

The emergence and spread of antibiotic resistance threatens to outpace the development of new antimicrobials, and slowing the spread of these organisms has become a priority. Among Enterobacteriaceae, the family of pathogens most frequently associated with health care–associated infections,[1] resistance to the broad-spectrum antimicrobials extended-spectrum cephalosporins and carbapenems has been driven largely by the spread of plasmid-mediated resistance genes encoding extended-spectrum β-lactamases (ESBLs) and carbapenemases, respectively. In the United States, ESBL-producing Enterobacteriaceae were first reported in 1988.[2] The emergence of these ESBL-producing isolates limited the options available for treatment, but these organisms remained susceptible to some first-line therapies, including carbapenems. In general, facilities independently selected approaches to control spread, which often included core infection control practices, such as hand hygiene, and placing patients with ESBL-producing strains in single rooms under Contact Precautions.

Enterobacteriaceae resistance to even broader spectrum antimicrobials, including carbapenems, was reported with increasing frequency beginning in 2001.[3] Rapid spread of these carbapenem-resistant Enterobacteriaceae (CRE) in parts of the United States and other countries[4,5] highlighted a need to more aggressively control CRE transmission. In 2009, CDC created CRE-specific guidance, which was endorsed by the Healthcare Infection Control Practices Advisory Committee.[6] This guidance included recommendations for additional interventions when CRE was identified at a health care facility, including laboratory surveillance of clinical cultures and targeted patient screening to identify health care contacts with asymptomatic colonization. This CRE-specific guidance was updated in 2013 and 2015 (https://www.cdc.gov/hai/organisms/cre/cre-toolkit/index.html) and was highlighted by CDC in a 2013 report.[7]

In 2017, CDC outlined a new effort to react rapidly to novel multidrug-resistant organisms;[8] this approach includes encouraging health care facilities and public health authorities to respond to single isolates of an emerging antibiotic-resistant pathogen. The strategy rests on these five pillars: 1) rapid detection of targeted pathogens and their resistance mechanisms, 2) on-site infection control assessments by trained experts to identify gaps in infection prevention, 3) screening of exposed contacts to identify asymptomatic colonization, 4) coordination of the response among facilities, and 5) continuing these interventions until transmission is controlled. Detection and control efforts can extend from the index facility to other facilities that share patients.

To support this approach, CDC established the Antibiotic Resistance Laboratory Network (ARLN) (https://www.cdc.gov/drugresistance/solutions-initiative/ar-lab-networks.html) to improve national capacity to rapidly detect and respond to antibiotic resistance. ARLN provides carbapenemase testing for two emerging antibiotic resistant pathogens, CRE and carbapenem-resistant Pseudomonas aeruginosa (CRPA), at 56 state and local public health laboratories and screening for asymptomatic CRE and CRPA carriage at seven regional laboratories.[9] Carbapenemase-producing strains were targeted for detection and response in part because of their previously demonstrated propensity for spread. CDC also expanded funding to state and local health departments to increase capacity and build expertise in responding to these and other emerging antibiotic resistance threats.

For this report, data from a national health care–associated infections surveillance system were reviewed to determine if the more directed approach applied for CRE was associated with differences in the percentage of Enterobacteriacae health care–associated infections that were CRE compared with those that had the ESBL phenotype. In addition, findings from the first 9 months of the enhanced response to emerging resistant organisms are described.

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Key Points

The emergence and spread of antibiotic resistance threatens to outpace the development of new antibiotics. Slowing the spread of emerging resistance is a CDC priority to protect persons and help slow the development of antibiotic resistance overall.

Infection data from the National Healthcare Safety Network from 2006–2015 were analyzed to calculate changes in the annual proportion of selected pathogens that were nonsusceptible to extended-spectrum cephalosporins (ESBL phenotype) or resistant to carbapenems (carbapenem-resistant Enterobacteriaceae [CRE]).

The percentage of ESBL phenotype Enterobacteriaceae decreased by 2% per year; by comparison, the CRE percentage decreased by 15% per year.

The proportion of Enterobacteriaceae infections that were CRE remained lower and decreased more over time than the proportion that were ESBL phenotype. This difference might be explained by the more directed control efforts implemented to slow transmission of CRE than those applied for ESBL-producing strains.

These data suggest that an early aggressive response, as outlined in CRE-specific infection prevention recommendations released beginning in 2009, can slow emergence and even decrease the occurrence of infections from resistant pathogens.

In 2017, CDC outlined a new effort to react rapidly to novel multidrug-resistant organisms; this approach includes encouraging health care facilities and public health authorities to respond to even single isolates of an emerging antibiotic-resistant pathogen.

From January to September 2017, carbapenemase testing was performed by the Antibiotic Resistance Lab Network for 4,442 CRE and 1,334 carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates; 32% and 1.9%, respectively were carbapenemase-producers. Among the carbapenemase-producing isolates, 221 (15.5%) expressed carbapenemases other than Klebsiella pneumoniae carbapenemase. Carbapenemases can make germs resistant to some of our most powerful drugs, carbapenems.